Figure 2.

Tree of human ATP-binding cassette domains. The evolution of the ABCB subfamily from within the ABCC subfamily, and the structural diversity of subfamily B is shown here. Each cluster of ABC domains within each subfamily, except for subfamily B, is collapsed to form a single, representative, branch; n-term: amino-terminal ABC; c-term: carboxy-terminal ABC. The phylogeny of ATP-binding cassettes from human ABC transporters was produced according the following procedure. Predicted amino-acid sequences were aligned using ClustalX [54]. Aligned sequences were used to generate matrices of mean distances among proteins, and these matrices were used to generate a phylogenetic tree according to the neighbor-joining algorithm [55], refined using the SPR branch-swapping technique under the minimum evolution criterion, implemented by PAUP*4.0b10 [56]. Bootstrapping [57] was used to determine the relative support for the various branches of the tree (1,000 replicates), and nodes with less than 50% support were collapsed to form polytomies. The structures of the proteins in which the domains are embedded are indicated according to the color scheme in Figure 1. It should be noted that branch lengths in the figures are not to scale and do not represent distances between protein sequences. The original alignment files are available as Additional data files 1-8.